title: Antigen-free adjuvant assists late effector CD4 T cells to transit to memory in lymphopenic hosts.
abstract: The events controlling the transition of T cells from effector to memory remain largely undefined. Many models have been put forth to account for the origin of memory precursors, but for CD4 T cells initial studies reported that memory T cells derive from IFN-γ-nonproducing effectors, whereas others suggested that memory emanates from highly activated IFN-γ-producing effectors. In this study, using cell proliferation, expression of activation markers, and production of IFN-γ as a measure of activation, we defined two types of effector CD4 T cells and investigated memory generation. The moderately activated early effectors readily transit to memory, whereas the highly activated late effectors, regardless of their IFN-γ production, develop minimal memory. Boosting with Ag-free adjuvant, however, rescues late effectors from cell death and sustains both survival and IFN-γ cytokine responses in lymphopenic hosts. The adjuvant-mediated memory transition of late effectors involves the function of TLRs, most notably TLR9. These findings uncover the mechanism by which late effector CD4 T cells are driven to transit to memory and suggest that timely boosts with adjuvant may enhance vaccine efficacy.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors.forename: F Betul
authors.initials: FB
authors.lastname: Guloglu
authors.forename: Jason S
authors.initials: JS
authors.lastname: Ellis
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wan
authors.forename: Mermagya
authors.initials: M
authors.lastname: Dhakal
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hoeman
authors.forename: Jason A
authors.initials: JA
authors.lastname: Cascio
authors.forename: Habib
authors.initials: H
authors.lastname: Zaghouani
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma; D008213:Lymphocyte Activation / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D007371:Interferon-gamma